rs2076605

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_022089.4(ATP13A2):c.3236-30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,587,734 control chromosomes in the GnomAD database, including 200,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14622 hom., cov: 30)

Exomes 𝑓: 0.50 ( 186033 hom. )

Consequence

ATP13A2
NM_022089.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.13

Publications

10 publications found

Variant links:

Genes affected

ATP13A2 (HGNC:30213): (ATPase cation transporting 13A2) This gene encodes a member of the P5 subfamily of ATPases which transports inorganic cations as well as other substrates. Mutations in this gene are associated with Kufor-Rakeb syndrome (KRS), also referred to as Parkinson disease 9. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Nov 2008]

ATP13A2 Gene-Disease associations (from GenCC):

Kufor-Rakeb syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Genomics England PanelApp, G2P, ClinGen
autosomal recessive spastic paraplegia type 78
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
parkinsonism due to ATP13A2 deficiency
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ATP13A2 links:

ENSG00000226526 (HGNC:):

ENSG00000226526 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 1-16986662-G-A is Benign according to our data. Variant chr1-16986662-G-A is described in ClinVar as Benign. ClinVar VariationId is 559000.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.523 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATP13A2	NM_022089.4 link	c.3236-30C>T		intron_variant	Intron 27 of 28	ENST00000326735.13	NP_071372.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP13A2	ENST00000326735.13 link	c.3236-30C>T		intron_variant	Intron 27 of 28	1	NM_022089.4	ENSP00000327214.8

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63323

AN:

151670

Hom.:

14617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.447

Gnomad ASJ

AF:

0.473

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.453

Gnomad FIN

AF:

0.473

Gnomad MID

AF:

0.415

Gnomad NFE

AF:

0.527

Gnomad OTH

AF:

0.431

GnomAD2 exomes

AF:

0.471

AC:

98011

AN:

208288

AF XY:

0.476

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.482

Gnomad EAS exome

AF:

0.296

Gnomad FIN exome

AF:

0.487

Gnomad NFE exome

AF:

0.524

Gnomad OTH exome

AF:

0.476

GnomAD4 exome

AF:

0.504

AC:

724300

AN:

1435946

Hom.:

186033

Cov.:

AF XY:

0.504

AC XY:

359756

AN XY:

713304

show subpopulations

African (AFR)

AF:

0.202

AC:

6657

AN:

32984

American (AMR)

AF:

0.477

AC:

19608

AN:

41124

Ashkenazi Jewish (ASJ)

AF:

0.484

AC:

12460

AN:

25730

East Asian (EAS)

AF:

0.308

AC:

11893

AN:

38640

South Asian (SAS)

AF:

0.473

AC:

39972

AN:

84570

European-Finnish (FIN)

AF:

0.486

AC:

22157

AN:

45588

Middle Eastern (MID)

AF:

0.492

AC:

2392

AN:

4864

European-Non Finnish (NFE)

AF:

0.527

AC:

580996

AN:

1102988

Other (OTH)

AF:

0.474

AC:

28165

AN:

59458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

21790

43580

65370

87160

108950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16522

33044

49566

66088

82610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.417

AC:

63340

AN:

151788

Hom.:

14622

Cov.:

AF XY:

0.413

AC XY:

30628

AN XY:

74170

show subpopulations

African (AFR)

AF:

0.218

AC:

9049

AN:

41420

American (AMR)

AF:

0.447

AC:

6822

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

1639

AN:

3468

East Asian (EAS)

AF:

0.281

AC:

1436

AN:

5118

South Asian (SAS)

AF:

0.453

AC:

2184

AN:

4818

European-Finnish (FIN)

AF:

0.473

AC:

4993

AN:

10552

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.527

AC:

35759

AN:

67842

Other (OTH)

AF:

0.426

AC:

897

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1731

3461

5192

6922

8653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.416

Hom.:

6374

Bravo

AF:

0.407

Asia WGS

AF:

0.342

AC:

1190

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 19, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 69% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 64. Only high quality variants are reported. -

Autosomal recessive spastic paraplegia type 78

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Kufor-Rakeb syndrome

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over